rs1553706799
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_138615.3(DHX30):c.2354G>A(p.Arg785His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R785C) has been classified as Pathogenic.
Frequency
Consequence
NM_138615.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHX30 | NM_138615.3 | c.2354G>A | p.Arg785His | missense_variant | 15/22 | ENST00000445061.6 | NP_619520.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHX30 | ENST00000445061.6 | c.2354G>A | p.Arg785His | missense_variant | 15/22 | 1 | NM_138615.3 | ENSP00000405620.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 04, 2017 | - - |
Neurodevelopmental disorder with severe motor impairment and absent language Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 27, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2023 | Published functional studies demonstrate a detrimental effect to protein function with reduced ATPase activity, a large number of cytoplasmic aggregates, and a reduced level of translation activity in HEK293T cells (Lessel et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28135719, 28191890, 34145223, 34020708, 29100085) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at